The Epstein-Barr virus LMP1 gene product induces A20 zinc finger protein expression by activating nuclear factor kappa B

• Published in: The Journal of biological chemistry Vol. 267; no. 34; pp. 24157 - 24160
• Main Authors: Laherty, C D, Hu, H M, Opipari, A W, Wang, F, Dixit, V M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 05-12-1992
• Subjects: Antigens, Viral - genetics; Biological and medical sciences; Blotting, Northern; Chloramphenicol O-Acetyltransferase - genetics; Chloramphenicol O-Acetyltransferase - metabolism; Fundamental and applied biological sciences. Psychology; Genes, Viral; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - immunology; Humans; Lymphoma, B-Cell; Membrane Proteins - genetics; Microbiology; NF-kappa B - metabolism; Promoter Regions, Genetic; Protein Binding; Recombinant Proteins - metabolism; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; RNA, Viral - genetics; RNA, Viral - isolation & purification; Transfection; Tumor Cells, Cultured; Viral Matrix Proteins; Virology; Zinc Fingers - genetics; Gammaherpesvirinae; Virus; Genetic transformation; Transcription; Tumor necrosis factor; Zinc finger structure; Herpesviridae; Activation; Epstein Barr virus; Transcription factor
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)35741-7

A20 is an inducible zinc finger protein that confers resistance to tumor necrosis factor alpha cytotoxicity. A survey of various
cell lines revealed that A20 was constitutively expressed in Epstein-Barr virus (EBV)-immortalized B-cells. Transfection experiments
demonstrated that the EBV latent membrane protein LMP1 induced A20 expression. LMP1 is a transforming protein of EBV that
has dramatic effects on cell growth, activation, and survival. An integral membrane phosphoprotein, LMP1 bears no homology
to other recognized membrane signaling molecules, and its signal transduction pathway is not known. However, studies using
the A20 promoter demonstrated that LMP1 transcriptionally activates the A20 gene through cis-acting kappa B sites. In addition,
electrophoretic mobility shift assays confirmed LMP1-inducible binding of an NF-kappa B-like factor to kappa B sequences within
the A20 promoter. This is the first report implicating NF-kappa B in signaling by LMP1, a fundamentally important viral transforming
protein.